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15/5/2020

Alkaptonuria and ochronosis

Author: Vanessa Ngan, Sta Writer, 2006. Images added February 2014.

Alkaptonuria and ochronosis — codes and concepts open

What is alkaptonuria and ochronosis?

Alkaptonuria is a rare genetic disease that is characterised by passing urine that becomes black when left
standing. The earliest sign of the condition is usually dark staining found in nappies or diapers of infants.

The most obvious sign in adults is a thickening and blue-black discolouration of the ear cartilage. This blue-
black discolouration of connective tissue (including bone, cartilage, and skin) caused by deposits of yellow
or ochre-coloured pigment is called ochronosis.

What causes alkaptonuria and ochronosis?

Alkaptonuria is an autosomal recessive inherited disorder, which means that two abnormal genes (one
from each parent) are needed to have the disease. The defect causes the body to produce insu cient
quantities of an enzyme called homogentisic acid oxidase. This enzyme normally breaks down a toxic
byproduct of tyrosine metabolism called homogentisic acid. Although some of this is excreted in urine,
small amounts remain in the body and slowly and progressively get deposited in bones and cartilage where
it turns into a pigmented polymeric material.

Ochronosis may also be caused by external agents. These may include:

Medications such as quinacrine and quinine

Deposits of phenol (carboxylic acid), used in the past to treat leg ulcers
Rarely, excessive use of hydroquinone (in this case, cartilage is not a ected).

Genetics of Alkaptonuria*

*Image courtesy Genetics 4 Medics

What are the clinical features of alkaptonuria and
ochronosis?
Most patients don't have any symptoms throughout childhood or early adult life and it is not until they
reach their 40's that other signs of the disease start appearing. One of the earliest signs is thickening of the
ear cartilage (the pinna feels noticeably thickened and exible). In addition the skin turns a blue-black
colour. Earwax is often reddish-brown or jet-black. Gradually patients will su er sore joints, leading to
arthropathy (joint disease characterised by swelling and enlarged bones). Many body parts become
a ected due to the build-up of pigment deposits in bones and cartilage.

Bones and cartilage of the lower back, knees, shoulders and hips are most a ected. Firstly patients
su er low back pain with sti ness, followed by knee, shoulder and hip pain over the next 10 years.
Cartilage becomes brittle and can break apart easily. In some cases this leads to spinal injuries such as
prolapsed intervertebral discs.
Deposits around the trachea (windpipe), larynx (voice box) and bronchi (air passages to the lungs) may
cause shortness of breath and di culty breathing.
Deposits around the heart and blood vessels can calcify (harden) and lead to atherosclerotic plaques
(hard spots in arteries).
Pigmentation of the sclera of the eye usually occurs early on. This does not a ect vision but appears as
brown or grey deposits on the surface of the eye.
Skin colour changes are most apparent on areas exposed to the sun and where sweat glands are
found. Areas most a ected include the cheeks, forehead, armpits and genital regions. The skin takes on
a blue-black speckled discolouration. Sweat produced has been found to stain clothes. Sometimes nails
can be a ected and turn a distinct brown colour.

Ochronosis following long-term use of hydroquinone

Ochronosis following Ochronosis following Dermoscopy of

long-term use of long-term use of ochronosis
hydroquinone hydroquinone

What is the treatment for alkaptonuria?

Alkaptonuria is a lifelong disease. There is no cure for the condition. If alkaptonuria is diagnosed early on in
life it is reasonable for patients to have a low-protein diet. This reduces the intake of amino acids
phenylalanine and tyrosine, which in turn reduces the amount of homogentisic acid produced. Although
not proven, this could potentially avoid or minimise complications later in life.

Vitamin C has been found to slow down the conversion of homogentisic acid to the polymeric deposits in
cartilage and bone. A dose of up to 1g/day is recommended for older children and adults. Nitisinone, an
enzyme inhibitor that mediates the formation of homogentisic acid is being used in restricted experimental
treatments.

Life expectancy is normal although patients may be at increased risk of heart conditions and may require
surgical treatments for spine, hip, knee and shoulder joint problems.
Exogenous cutaneous ochronosis has been successfully treated by laser.

Related information
 

References
Textbook of Dermatology. Ed Rook A, Wilkinson DS, Ebling FJB, Champion RH, Burton JL. Fourth
edition. Blackwell Scienti c Publications.
Alkaptonuria #203500OMIM – Online Mendelian Inheritance in Man

On DermNet NZ
Hydroquinone
Bleaching creams

Other websites
Alkaptonuria – Medscape Reference
Alkaptonuria Society
Alkaptonuria (AKU) Society UK
Alkaptonuria – GeneTests GeneReviews

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